Tumor-reactive TCRs within exhausted TILs reveal cancer type-specific immune landscapes in renal cell carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) presents a unique immunological paradox: abundant CD8⁺ tumor-infiltrating lymphocytes (TILs) correlate with poor prognosis. To clarify their functional status and therapeutic potential, we performed single-cell transcriptomic profiling of TILs from 15 patients with ccRCC and functionally validated dominant T cell receptor (TCR) clonotypes using autologous tumor-derived organoids. Single-cell RNA sequencing revealed dynamic shifts in T cell composition, with effector and progenitor-exhausted CD8⁺ T cells declining and terminally exhausted CD8⁺ and regulatory CD4⁺ T cells enriched in advanced tumors. Despite this exhausted phenotype, in an exploratory analysis with five patients, approximately half of the top

SUBMITTER: Komahashi M 

PROVIDER: S-EPMC12894369 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature